OMIA:000328-9940 : Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-related in Ovis aries
In other species: cattle , domestic cat , dog
Categories: Integument (skin) phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 225410 (trait) , 604539 (gene)
Links to MONDO diseases:
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2012
Species-specific name: Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-related; Ehlers-Danlos syndrome, type VII (Dermatosparaxis); dermatosparaxis
Species-specific symbol: dEDS; EDS
Species-specific description: Although evidence was incomplete, it appeared for many years that this disorder in sheep is due to a mutation in the gene for the enzyme procollagen I amino proteinase, this being the enzyme responsible for removing "surplus" amino acids from the N-terminal end of procollagen-I molecules.
This phene has been renamed from "Ehlers-Danlos syndrome, type VII (Dermatosparaxis)" to "Dermatosparaxis Ehlers-Danlos syndrome (dEDS), ADAMTS2-related" in OMIA on the basis of the review on human Ehlers-Danlos syndromes by Malfait et al. (2020) [2/6/2022].
Molecular basis: In 2012, Zhou et al. showed that the situation described in the Species-specific section above is, indeed, the case: the disorder in affected White Dorper sheep from New Zealand is due to a nonsense mutation (c.421G>T) in exon 2 of the gene encoding that procollagen proteinase. Unhelpfully, the gene is called ADAM metalloproteinase with thrombospondin type I motif, 2 (ADAMTS2).
Monteagudo et al. (2015) reported a second likely causal variant (c.805G>A; p.Val269Met) in the same gene, in an affected White Dorper from Spain.
Joller et al. (2017) reported an affected White Dorper in Switzerland with the same variant as reported in the New Zealand White Dorpers (now c.424G>T; p.Glu142*). This is consistent with the recent migration of White Dorpers from South Africa to many other countries.
Breed: Dorper (Sheep) (VBO_0001397).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ADAMTS2||ADAM metallopeptidase with thrombospondin type 1 motif 2||Ovis aries||5||NC_056058.1 (1787346..2042368)||ADAMTS2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|318||Dorper (Sheep)||Ehlers-Danlos syndrome, type VII (Dermatosparaxis)||ADAMTS2||nonsense (stop-gain)||Naturally occurring variant||Oar_rambouillet_v1.0||5||g.1938399G>T||c.424G>T||p.(E142*)||XM_012156230:c.424G>T, XP_012011620:p.Glu142* (Joller et al., 2017)||2012||22497338||The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.|
|857||Dorper (Sheep)||Ehlers-Danlos syndrome, type VII (Dermatosparaxis)||ADAMTS2||nonsense (stop-gain)||Naturally occurring variant||Oar_rambouillet_v1.0||5||g.2088231G>A||c.805G>A||p.(V269M)||XM_012156230:c.805G>A, XP_012011620:p.Val269Met (Joller et al., 2017)||2015||25354687||The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2021||Roberts, J.H., Halper, J. :|
|Connective tissue disorders in domestic animals. Adv Exp Med Biol 1348:325-335, 2021. Pubmed reference: 34807427 . DOI: 10.1007/978-3-030-80614-9_15.|
|2020||Malfait, F., Castori, M., Francomano, C.A., Giunta, C., Kosho, T., Byers, P.H. :|
|The Ehlers-Danlos syndromes. Nat Rev Dis Primers 6:64, 2020. Pubmed reference: 32732924 . DOI: 10.1038/s41572-020-0194-9.|
|2018||Nogueira, J.F., Borges, A.S., de Andrade, D.G.A., Bezerra, F.C.M., de Oliveira, J.P., Cunha, S.M.F., Gouveia, G.V., Gouveia, J.J.D. :|
|Deepening the knowledge about dermatosparaxis in Brazilian White Dorper population: Basis for the development and implementation of a genetic disease eradication program in sheep Livestock Science 217:162-166, 2018. DOI: 10.1016/j.livsci.2018.10.006.|
|2017||Joller, S., Berenguer Veiga, I., Drögemüller, C. :|
|Dermatosparaxis in White Dorper sheep: confirmation of a causative nonsense mutation in ADAMTS2. Anim Genet 48:729-730, 2017. Pubmed reference: 28856769 . DOI: 10.1111/age.12591.|
|2016||Andrade, D.G.A., Dalanezi, F.M., Trecenti, A.S., Cunha, P.H.J., Borges, A.S., Oliveira, J.P. :|
|Prevalence study of SNP c.421G > T in the ADAMTS2 gene responsible for dermatosparaxis in White Dorper sheep in Brazil Pesquisa Veterinaria Brasileira 36:73-76, 2016. DOI: 10.1590/S0100-736X2016000200002.|
|Gouveia, J.J.D., Cunha, S.M.F., de Almeida, E.M., Nogueira, J.F., Souza, J.L.P., Menezes, D.R., Gouveia, G.V. :|
|Molecular and genealogical analyses reveal multiple sources of the mutation associated with dermatosparaxis in Brazilian White Dorper sheep Small Ruminant Research 140:46-49, 2016. DOI: 10.1016/j.smallrumres.2016.05.014.|
|2015||Monteagudo, L.V., Ferrer, L.M., Catalan-Insa, E., Savva, D., McGuffin, L.J., Tejedor, M.T. :|
|In silico identification and three-dimensional modelling of the missense mutation in ADAMTS2 in a sheep flock with dermatosparaxis. Vet Dermatol 26:49-52, e15-6, 2015. Pubmed reference: 25354687 . DOI: 10.1111/vde.12178.|
|2012||Zhou, H., Hickford, J.G., Fang, Q. :|
|A premature stop codon in the ADAMTS2 gene is likely to be responsible for dermatosparaxis in Dorper sheep. Anim Genet 43:471-3, 2012. Pubmed reference: 22497338 . DOI: 10.1111/j.1365-2052.2011.02275.x.|
|2011||Vaatstra, B., Halliday, W.D., Waropastrakul, S. :|
|Dermatosparaxis in two white Dorper lambs. N Z Vet J 59:258-60, 2011. Pubmed reference: 21851305 . DOI: 10.1080/00480169.2011.596183.|
|1993||Lapiere, C.M., Nusgens, B.V. :|
|Ehlers-Danlos syndrome type VII-C, or human dermatosparaxis: the offspring of a union between basic and clinical research Archives of Dermatology 129:1316-1319, 1993. Pubmed reference: 8215498 .|
|1992||Nusgens, B.V., Verellen-Dumoulin, C., Hermanns-Le, T., De Paepe, A., Nuytinck, L., Pierard, G.E., Lapiere, C.M. :|
|Evidence for a Relationship Between Ehlers-Danlos Type-VII-C in Humans and Bovine Dermatosparaxis Nature Genetics 1:214-217, 1992. Pubmed reference: 1303238 . DOI: 10.1038/ng0692-214.|
|1991||Ramshaw, J.A., Mitrangas, K., Bateman, J.F. :|
|Heterogeneity in dermatosparaxis is shown by contraction of collagen gels. Connect Tissue Res 25:295-300, 1991. Pubmed reference: 2060304 .|
|1990||Basrur, P.K., Yadav, B.R. :|
|Genetic Diseases of Sheep and Goats Veterinary Clinics of North America-Food Animal Practice 6:779-802, 1990. Pubmed reference: 2245374 .|
|1988||Mauch, C., Mark, K. van der, Helle, O., Mollenhauer, J., Pfaffle, M., Krieg, T. :|
|A defective cell surface collagen-binding protein in dermatosparactic sheep fibroblasts Journal of Cell Biology 106:205-211, 1988. Pubmed reference: 2828379 .|
|van Halderen, A., Green, J.R. :|
|Dermatosparaxis in White Dorper sheep. J S Afr Vet Assoc 59:45, 1988. Pubmed reference: 3361559 .|
|1986||van Weeren-Keverling Buisman, A., Koeman, J.P. :|
|[A form of dermatosparaxis in a Texel lamb]. Tijdschr Diergeneeskd 111:173-7, 1986. Pubmed reference: 3952722 .|
|1985||Bavinton, J.H., Peters, D.E., Ramshaw, J.A. :|
|A morphologic study of a mild form of ovine dermatosparaxis. J Invest Dermatol 84:391-5, 1985. Pubmed reference: 3998490 .|
|1984||Ramshaw, J.A. :|
|A mild form of ovine dermatosparaxis. Coll Relat Res 4:441-51, 1984. Pubmed reference: 6441674 .|
|1983||Ramshaw, J.A., Peters, D.E., Jones, L.N., Badman, R.T., Brodsky, B.B. :|
|Ovine dermatosparaxis. Aust Vet J 60:149-51, 1983. Pubmed reference: 6412675 .|
|1982||Wiestner, M., Rohde, H., Helle, O., Krieg, T., Timpl, R., Müller, P.K. :|
|Low rate of procollagen conversion in dermatosparactic sheep fibroblasts is paralleled by increased synthesis of type I and type III collagens. EMBO J 1:513-6, 1982. Pubmed reference: 7188350 .|
|1976||Becker, U., Timpl, R. :|
|NH2-terminal extensions on skin collagen from sheep with a genetic defect in conversion of procollagen into collagen. Biochemistry 15:2853-62, 1976. Pubmed reference: 949480 .|
|1974||Fjølstad, M., Helle, O. :|
|A hereditary dysplasia of collagen tissues in sheep Journal of Pathology 112:183-188, 1974.|
|1972||Helle, O., Nes, N.N. :|
|A hereditary skin defect in sheep. Acta Vet Scand 13:443-5, 1972. Pubmed reference: 4673742 .|
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